tbuckley/cabot-search huggingface dataset:
Abstract 11464: Spectrum and Associated Factors for Coronary Artery Involvement in Kawasaki Disease versus Multisystem Inflammatory Syndrome in Children Associated With Covid-19
Authors: Simon Lee, Ashraf S Harahsheh, Michael A Portman, Marianna Fabi, Supriya Jain, Mona El Ganzoury, Audrey Dionne, Nilanjana Misra, Todd Nowlen, Matthew Elias, Elisa Fernandez-Cooke, Jacqueline R Szmuszkovicz, William Orr, Dongngan Truong, Kimberly E McHugh, Nadine Choueiter, Surya Shah, Cedric Manlhiot, Pedrom Farid, Brian W McCrindle
Journal: Circulation (2022)

Introduction: Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 share clinical features and are both associated with coronary artery (CA) involvement. Methods: From January 2020 through January 2022, n=2566 contemporaneous KD, MIS-C and acute COVID-19 pediatric patients from 39 sites in 8 countries were enrolled into the International KD Registry. The study population was confined to 875 MIS-C patients meeting CDC criteria with confirmed or probable COVID-19 infection, and 492 KD patients meeting AHA guideline criteria without COVID-19 infection who had sufficient echo data. CA involvement was defined by maximum Z score in any branch at any timepoint (maxCAZ). Associated factors for each diagnosis were determined with multivariable logistic regression for maxCAZ&gt;2. Results: Median maxCAZ was higher for KD (+1.43) vs MIS-C patients (+1.33; p=0.004). The groups did not differ regarding the incidence of maxCAZ&gt;2 (KD 26% vs MIS-C 24%; p=0.42), although MIS-C patients had less severe Z score categories of involvement (FIGURE). In univariate analyses, higher peak troponin I (p&lt;0.05) and NTproBNP (p=0.06) were associated with maxCAZ&gt;2 for MIS-C but not KD patients. Lower LV ejection fraction was likewise associated with maxCAZ&gt;2 for MIS-C (p=0.009) but not KD patients. For KD patients, independent factors associated with maxCAZ&gt;2 were male sex, age &amp;lt;6 months, greater total days of fever, shock presentation, and higher peak platelet count and CRP (c-statistic 0.69). In contrast, for MIS-C patients the only independent factor associated with maxCAZ&gt;2 was male sex (c-statistic 0.56). Conclusions: Compared to KD patients, MIS-C patients have a similar incidence but lesser severity of CA involvement with few associated factors, male sex being the only one in common. CA involvement was significantly associated with higher cardiac biomarkers and lower LV ejection fraction for MIS-C patients only.
Abstract 11642: Biologic Associations of the Senescence-Associated Secretory Phenotype (SASP) in Heart Failure (HF): Insights From Plasma Proteomics
Authors: Chenao Qian, Payman Zamani, Oday Salman, Qasim Jehangir, Jordana Cohen, Kushan Gunawardhana, Danielle Greenawalt, Lei Zhao, Ching-Pin Chang, David A Gordon, Francisco Ramirez-Valle, Thomas P Cappola, Julio A Chirinos
Journal: Circulation (2022)

Background: Cell senescence is involved in various age-related pathologies, including HF. The SASP is a characteristic secretory phenotype from senescent cells. We assessed biologic pathways associated with the SASP in human HF using a plasma proteomics approach. Methods: We measured 25 known SASP proteins among 2248 Penn HF Study (PHFS) participants using the SomaScan V4 assay. Factor analysis was used to extract the common variance among these proteins. Linear regression was used to assess the relationship of each factor to 4,746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Results: Two underlying SASP factors were identified: Factor 1 was mainly represented by with matrix metallopeptidase 2, Tissue inhibitor of metalloproteinase 2 and Insulin Like Growth Factor Binding Protein 7. Factor 2 was correlated with cystatin C, Growth/differentiation factor-15 and Insulin-like Growth Factor Binding Protein-2. Both factors were associated with older age, male sex, lower BMI, higher prevalence of diabetes, higher prevalence of atrial fibrillation, lower estimated glomerular filtration rate and more advanced NYHA class. There was a lower prevalence of HF with recovered EF (as opposed to HF with reduced EF) among participants with higher levels of factor 1, but the prevalence of HF with preserved EF did not differ accordingly to levels of either factor. Factors 1 and 2 were associated with 1245 and 1509 proteins respectively. Both factors were associated with the coagulation system, complement system, acute phase response signaling, and retinoid X receptor (RXR) pathways that regulate cell metabolism ( Figure ). Conclusion: Higher levels of SASP are associated with older age, lower renal function and metabolic abnormalities in HF. Lower levels of SASP are associated with the presence of a recovered EF but not a preserved EF. Biologic pathways associated with SASP are predominantly related to inflammation and metabolic regulation.
Abstract 11573: Refractory Ventricular Tachyardia Storm: Treatment With Sympathetic Denervation in Patient With Non-Ischemic Cardiomyopathy
Authors: Mohammad Fahad Salam, Adolfo Martinez Salazar, Shakeel Jamal, Abdullah Al-abcha, Yasser Radwan, Ali Sheikh
Journal: Circulation (2022)

Introduction: Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia commonly present in cardiomyopathy. Implantable cardioverter-defibrillator (ICD) placement can decrease mortality in patients with VT. However, when an ICD shocks it can cause direct myocardial injury, contraction band necrosis, fibrosis, and significant morbidity. Antiarrhythmic medications and catheter ablation can decrease arrhythmia burden and ICD shocks. Cardiac sympathetic denervation has been effective in a few refractory cases, but prospective data is scarce, especially in non-ischemic cardiomyopathy. Case description We present the case of a 59-year-old gentleman with a past medical history of hypertension, diabetes, hypothyroidism, atrial fibrillation, and non-ischemic cardiomyopathy, who presented to the hospital with recurrent ICD shocks. The patient had an ICD placed due to an episode of non-sustained VT resulting in presyncope. The patient had an arrhythmia-free period of 10 years followed by frequent VT. He was managed in the outpatient setting with amiodarone, dofetilide, and mexiletine which did not suppress his arrhythmia burden. Cardiac MRI showed multi-segment transmural late gadolinium enhancement consistent with a non-ischemic pattern. He underwent three endocardial and epicardial ablations over eight months before this admission. He was started on amiodarone and lidocaine infusions. With his history of recurrent VT despite multiple ablations, the patient underwent bilateral thoracoscopic sympathetic denervation. He was discharged from the hospital six days post-op without any episodes of VT. His latest ICD check which was ten months post-operatively did not show any VT or VT-induced ICD shock. Conclusion VT storm may be associated with a catecholaminergic surge and be refractory to traditional therapy. Due to this, sympathetic denervation is a viable option to prevent morbidity of frequent defibrillator therapy. This case highlights the utility of sympathetic denervation as a treatment of refractory ventricular arrhythmias in non-ischemic cardiomyopathy.
Abstract 11618: Angiopoietin-2 is Associated With Capillary Leak and Complications After Cardiac Surgery
Authors: Jakob Wollborn, Zilu Zhang, Samuel Justice, Daniel Reker, J Daniel Muehlschlegel, Ulrich Goebel, Felix Ulbrich
Journal: Circulation (2022)

Introduction: Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. Hypothesis: Markers of endothelial injury and inflammation are associated with capillary leak (CLS), ultimately increasing the risk of perioperative complications. Methods: In a prospective, observational trial 405 cardiac surgery patients were evaluated using daily body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of biomarkers. Multivariable models and machine learning (ML) were used to study the association of angiopoietin-2 (Ang-2) with extracellular water (ECW) as well as common complications after cardiac surgery. Results: Across all surgical groups, ECW increased postoperatively (20±6 preoperatively to 29±7L on POD2; P &lt;0.001). Concomitantly, the levels of Ang-2 rose, showing a strong correlation based on the time points of measurements (r=0.959, P =0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of CLS were increased. After accounting for common risk factors of edema formation in cardiac surgery, we found a significant association of Ang-2 and ECW (Table 1). Furthermore, high Ang-2 patients showed an increased odds for developing acute kidney injury (OR 1.095 [1.032-1.169]; P =0.004), and high Ang-2 was associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. ML predicted postoperative complications well if CLS was added to standard risk factors. Conclusions: CLS is a relevant problem after cardiac surgery. Ang-2 in combination with ECW shows promising potential to reliably anticipate CLS and postoperative complications after cardiac surgery.
Abstract 11156: Over Time, Heart Failure Symptoms Worsen Depression
Authors: Laurie Abbott, Lucinda J Graven, Glenna Schluck
Journal: Circulation (2022)

Introduction: Heart failure (HF) is a global health problem, contributing to increases in hospital readmission rates, high health care costs, and increased morbidity and mortality. HF symptoms can be difficult to manage and lead to depression. Purpose: To examine the impact of a nurse-led, telephone, coping intervention and HF symptoms on depression in patients with HF. Methods: A 3-group randomized controlled pilot study was conducted with 107 HF patients to test the effectiveness of a 12-week telephone-based coping intervention for HF symptoms. The intervention group (n = 34) received 1 home visit, weekly (1st month), and biweekly (months 2-3) telephone calls. The attention group (n = 38) received sham calls on a similar pattern as the intervention group. All groups received usual care, with the control group (n = 35) receiving usual care only. HF patients were 61 years old, on average; 54.2% male; 54.2% African American; and 43.9% NYHA II. Data were collected at baseline, 5, 9, and 13 weeks on social support (Interpersonal Support Evaluation List), problem-solving (Social Problem-Solving Inventory Revised-Short), HF symptoms (Heart Failure Symptom Survey), and depression (Center for Epidemiological Studies-Depression scale). Linear mixed modeling was implemented to examine the effect of the intervention and HF symptoms on depression over time, controlling for social support and problem-solving. Results: Sixty-four patients completed the study (18 intervention; 24 attention; 22 control). No significant between-group differences in sociodemographic characteristics, HF symptoms, or depression was noted at baseline. There was no significant intervention effect over time on depression. However, experiencing HF symptoms over time contributed to worse depression across all groups. Conclusions: Experiencing HF symptoms can lead to worsened depression over time. Interventions that improve self-management of HF symptoms can potentially be effective in reducing depression in HF patients.
Abstract 11566: Distribution and New Function of Na, K-ATPase and Its Phosphoprotein Regulator Phospholemman in Cardiac Myocytes
Authors: Jin Guo, Yen L Sung, Peng-Sheng Chen, Zhenhui Chen
Journal: Circulation (2022)

Introduction: Na, K-ATPase (NKA), regulated by phosphoprotein phospholemman (PLM), contributes to excitation-contraction via the Na,Ca-exchanger at cardiac T-tubules (TTs). It is known that the intercalated discs (IDs) contain concentrated specific Na channels and K channels, that rely on ion gradients set by NKA. Yet, the coordinated trafficking and localization of NKA and PLM in cardiomyocytes (CMs) remains incompletely understood, Hypothesis: NKA and PLM are concentrated in the ID and essential for cardiac conduction. Methods: We have made five antibodies (Abs) that specifically identify PLM (B8, PLM-N-term, and PLM-C-term) or NKA (NKA-α1 and Pan-α, recognizing both α1 and α2 subunits of NKA). Confocal immunofluorescence assays were used to determine the intracellular distribution of PLM and NKA. Optical mapping studies were performed in rabbit hearts. Results: These five Abs all displayed specific fluorescence signals in dog CMs that were more intense at the IDs than TTs. These signals were eliminated by competing peptides. B8 and NKA-α1 signals highly overlapped, with similar intensity ratios between ID and TT at ~3. Immunostaining of connexin 43, γ-catenin, or N-cadherin confirmed the co-localization of NKA and PLM to the ID. PLM and NKA co-enriched with ID protein markers in sarcolemma/ID membrane preparations. To corroborate the localization of PLM at the ID, we expressed dog PLM in rat CMs. By 30h post-infection, B8 detected newly synthesized dog PLM that paralleled the pattern of its steady-state distribution in tissue, with concentrated protein apparent at IDs (B8 fluorescence intensity ratio of ID/TT = 2.6 ± 0.5, 50CMs). Nocodazole prevented newly-made dog PLM trafficking to ID. Finally, optical mapping studies showed that the NKA inhibitor ouabain and digoxin significantly increased activation times in a dose-dependent manner (n=5 and 4 rabbits, respectively). Conclusions: The α1 subunit of NKA and PLM are each expressed at a ~3X higher concentration in ID compared to TT in CMs, contributing to cardiac conduction. Mechanisms of PLM and NKA protein trafficking to the two disparate subcellular sites, and associated effects of PLM regulation by adrenergic signaling, provide important new insights into the physiology of cardiac conduction.
Abstract 11354: Role of PCSK9 Inhibitors in Acute Coronary Syndromes - A Pilot Study
Authors: Mahmoud Abdelnabi, Juthipong Benjanuwattra, Yehia Saleh, Gaspar Del Rio-Pertuz, Natnicha Leelaviwat, Abdallah Almaghraby
Journal: Circulation (2022)

Introduction: The proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have been guideline-approved for intolerant patients to statin therapy or unable to achieve target LDL levels with maximally tolerated therapies. The study aimed to determine whether early initiation of PCSK9 inhibitor with statin therapy in acute coronary syndromes (ACS) patients is beneficial in relation to low-density lipoprotein (LDL) reduction and short-term cardiovascular outcomes. Methods This pilot study included eighty ACS patients randomized to receive either PCSK9 inhibitor (Evolocumab) with statin therapy (n=40) or statin monotherapy (n=40). Patients were followed up for 6 months to assess for LDL levels, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (MACE) (a composite of myocardial infarction, heart failure, and cardiovascular death). Results Eighty patients with ACS (mean age 59±11 years, 66.3% male) had LDL and LVEF measured at baseline, 3 months, and 6 months. There was no difference between baseline LDL levels (153.1±39.5 vs 146.1±32, p=0.39). LDL levels in PCSK9 inhibitor/statin group were significantly lower at 3 months and 6 months compared to statin monotherapy (76.2±27.7 vs 118.6±31, p&lt;0.0001 and 78.2±22.1 vs 103.7±22.5, p&lt;0.0001, respectively). There was no significant difference between incidences of cardiovascular death (1 vs 3, p=0.31) and MACCE (4 vs 6, p=0.5) between both groups at 6-month follow-up. Conclusion The early initiation of PCSK9 inhibitors/statin combination therapy in ACS patients was associated with a significant reduction of LDL levels at 3 and 6 months yet there was no significant difference in relation to short-term cardiovascular outcomes at a 6-month follow-up. Further research is required to determine whether early initiation of PCSK9 inhibitors in combination with statins or as monotherapy in ACS patients can be associated with improved short or long-term cardiovascular outcomes.
Abstract 11305: CSL112 (Apolipoprotein A-I (Human)) Infusion in Post Myocardial Infarction Patients Promotes Hepatocyte Cholesterol Uptake Ex Vivo
Authors: Elena Velkoska, Brandon Greene, Heidi L Collins, Steven Adelman, Jenny Mears, Danielle Duffy, C. Michael Gibson, Svetlana Diditchenko, Bronwyn A Kingwell
Journal: Circulation (2022)

Background: Cholesterol efflux capacity (CEC) is inversely related to incident cardiovascular events. CSL112 (apoA-I (human)) infusion rapidly and robustly increases CEC in AMI patients, but it is unknown whether this translates to increased hepatocyte cholesterol uptake, the subsequent step in reverse cholesterol transport. Purpose: To determine whether CSL112 increases cholesterol uptake by hepatocytes when administered post AMI. Methods: Patients from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo, 2g or 6g CSL112 post AMI. Serum samples from a subset of subjects (n=15 per group) were studied ex vivo . Firstly, CEC was assessed using J774 macrophages loaded with labelled [ 3 H]cholesterol tracer. Cholesterol uptake media (200μL) was then collected and applied to Fu5AH hepatocytes for assessment of labelled cholesterol uptake. Results: CSL112 infusion dose-dependently increased hepatocyte cholesterol uptake, with the 6g dose inducing a &lt; 2-fold increase at the end of infusion (2 h), and sustained elevation above baseline at 24 - 48 h (Fig 1A). Hepatocyte cholesterol uptake across all dose groups and timepoints was strongly correlated with total CEC (r=0.949; p&lt;0.001; Fig 1B) and plasma apoA-I (r=0.746; p&lt;0.001). Conclusion: Infusion of CSL112 increased uptake of cholesterol into hepatocytes in direct proportion to increased CEC and apoA-I levels. This study demonstrates that the rapid, robust increase in CEC induced by CSL112 is also associated with substantial elevation in hepatocyte cholesterol uptake using an assay which models the final step in reverse cholesterol transport prior to cholesterol excretion in bile. Figure 1: (A) Effect of CSL112 on hepatocyte cholesterol uptake (mean ± SEM). (B) Intra-subject correlation using individual data points across all timepoints.
Abstract 11219: Female Patients Attending Female Cardiologist-Led Heart Clinic in Iraq: Clinical Landscape and Echocardiographic Data
Authors: Zainab A Dakhil, Moatamn Skuk
Journal: Circulation (2022)

Introduction: In Iraq, traditional and tribal rules prevent many women from having access to healthcare unless being managed exclusively by female doctors. So, lack of female cardiologists (FC) in Iraq deprived many women from proper cardiovascular care.Considering the absent Women′s Heart Clinics in Iraq and lack of data on female cardiac patients,we sought to provide data regarding demographic and echocardiographic characteristics of women attending a female cardiologist-led heart clinic (FC-LHC) in a first report from Iraq Methods: Women who attended a FC-LHC were included, clinical and echocardiographic characteristics were recorded. Results: n=213, mean age (46.5±16.6)year.Hypertension (HT) and dyslipidemia were most reported risk factors.History of gestational HT was most common sex-specific risk factor (figA).Women′s comorbidities differs with their social status as HT, DM, IHD and dyslipidemia were highest in widowed women (91.3%, 43.5%, 21.7% and 39.1% respectively). Consuming fast food≥4/week was highest in divorced (33.3%) and single women (23.1%). OCP was used by 5.2% of women; in general and 10.3% of married women at reproductive age; in particular. Prevalence of DM,IHD and LV dysfunction differs according to women′s education (figB). Palpitation (46.5%) and dyspnoea (30%) were most common presentations. Cardio-Obstetric and Cardio-Oncology services were offered in 5.2% and 5.6% respectively (figC). LV diastolic dysfunction and mitral regurgitation were most common echocardiographic abnormalities (figD). Conclusion: Younger women&lt;65 years were more frequently attending FC-LHC.Prior history of gestational HT was the commonest sex-specific cardiovascular risk factor. Increasing diversity in cardiology workforce and establishing Women′s Heart Clinics that include FC are crucial in Iraq to promote focused cardiovascular care and education and to provide data for sex-specific research in cardiovascular management and outcomes
Abstract 11138: Short-Term Outcomes in Patients With a St-Elevation Myocardial Infarction and Concomitant Lung Cancer
Authors: Ahmad Gill, Omar Al-Taweel, Emily He, Mohammad Jaradat, DALIA HAWWASS, Chowdhury Ahsan
Journal: Circulation (2022)

Introduction: Patients with a ST-Elevation Myocardial Infarction (STEMI) and concomitant lung cancer are an understudied cohort. In this study, we explore the in-hospital outcomes of STEMI patients with and without lung cancer. Methods: We queried the National Inpatient Sample database (2016-2019) to identify patients admitted with a principal diagnosis of STEMI and secondary diagnosis of lung cancer. We conducted propensity score matching using a greedy nearest neighbor 1:1 model. Multivariable logistic regression was used to compare mortality. Results: 7020 patients met our inclusion criteria. Patients with a STEMI and lung cancer had 1.84 times higher odds of suffering in-hospital mortality compared to STEMI patients without lung cancer (aOR 1.84, 95% CI: 1.55-2.17; p &lt; 0.001). When separated by race, STEMI patients with lung cancer had a higher mortality rate amongst White (11.5% vs 6.5%, p &lt; 0.001) and Black (11.9% vs 6.5%, p = 0.03, Figure 1) patients. STEMI patients with lung cancer were less likely to undergo percutaneous coronary intervention (22.3% vs 32.0%, p &lt; 0.001). There was no difference in intraoperative and postoperative cardiac arrest, cerebral infarction and respiratory failure. Additionally, STEMI patients with lung cancer had longer hospital stays (4.9 days vs 4.4 days, p &lt; 0.001, Table 1). Conclusions: Patients with a STEMI and lung cancer had higher odds of suffering in-hospital mortality compared to patients with a STEMI without lung cancer. Our findings emphasize the importance of risk-benefit analysis and collaborative discussion amongst the care team prior to choosing the appropriate treatment modality.